Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast (Harrison's Principles of Internal Medicine, 14/e, McGraw-Hill Companies, New York, 1998). Although much progress has been made toward understanding the biological basis of breast cancer and in its diagnosis and treatment, it is still one of the leading causes of death among women in the United States. Inherent difficulties in the diagnosis and treatment of cancer include among other things, the existence of many different subgroups of cancer and the concomitant variation in appropriate treatment strategies to maximize the likelihood of positive patient outcome.
The traditional method of breast cancer diagnosis and staging is through the use of biopsy examination, for example, histological examination of a tissue sample. Once a diagnosis is made, the treatment options traditionally include surgical intervention, chemotherapy, radiotherapy, and adjuvant systemic therapies. Surgical therapy may be lumpectomy or more extensive mastectomy. Adjuvants may include but are not limited to chemotherapy, radiotherapy, and endocrine therapies such as castration; administration of LHRH agonists, antiestrogens, such as tamoxifen, high-dose progestogens; adrenalectomy; and/or aromatase inhibitors (Harrison's Principles of Internal Medicine, 14/e, McGraw Hill Companies, New York, 1998).
An accurate diagnostic test for breast cancer is critical to allow patients to receive appropriate cancer treatment when such treatment may be less invasive (e.g. the cancer is smaller) and has a high likelihood of successfully eliminating the cancer. Currently available tests are useful, but may require expensive procedures, such as mammography, followed by surgical biopsy. A less invasive and less expensive diagnostic test for breast cancer would allow better access to diagnostic services for more women, and may increase the likelihood of successful outcome for breast cancer patients.
Another element of key importance in the successful treatment of breast cancer is the selection and implementation of an appropriate combination of therapeutic approaches. For example, depending on a breast cancer patient's prognosis, therapy may include surgical intervention in combination with adjuvant therapy or it may only include surgical intervention. In addition, for some patients pretreatment with chemotherapy or radiotherapy is utilized prior to surgical intervention, but in other patients adjuvant therapies are used following surgical intervention.
Determination of appropriate treatment for an individual cancer patient is complex with a wide variety of treatments and possible treatment combinations. For example, chemotherapy is a common method of cancer treatment, with more than 50 different chemotherapeutic agents available. These therapeutic agents can be used in a wide range of dosages both singly and in combinational therapies with other chemotherapeutic agents, surgery, and/or radiotherapy. The available methods for designing strategies for treating breast cancer patients are complex and inexact. Therefore it is important to monitor the impact of the treatment on the cancer. By monitoring the effectiveness of a treatment strategy, the treatment can be modified as necessary to improve the chances for long-term patient survival.
Because of the importance of selecting appropriate treatment regimens for breast cancer patients, and for following their progress, the development of methods to monitor treatment as well as to sensitively diagnose breast cancer is of key interest to those in the medical community and their patients. Although available diagnostic procedures for breast cancer may be partially successful, the methods for detecting breast cancer and monitoring its treatment remain unsatisfactory. There is a critical need for diagnostic tests that can detect breast cancer at its early stages, when appropriate treatment may substantially increase the likelihood of positive outcome for the patient. It is also important that breast cancer treatment be monitored to allow the treatment to be adapted as necessary to best serve the patient's clinical needs. Such diagnostic and monitoring methods will enable medical care professionals to identify breast cancer, select optimal treatment regimens for individual patients, and to assess the cancer before, during, and after treatment.